Effect of Erythropoietin on Metabolic and Contractile Functions of Soleus Muscle in Type I Diabetic Rats.

Abstract

Diabetes mellitus has been linked  with specific morphological and metabolic abnormalities  in  skeletal  muscle  in  a  fiber specific manner. Erythropoietin (EPO) is a glycoprotein hormone that regulates the development of erythrocytes through binding to a high affinity receptor expressed in erythroid progenitor cells.EPO receptor expression in non-hematopoietic tissue, including skeletal muscle progenitor cells, raises the possibility of a role for EPO beyond erythropoiesis.  So the aim of the present study was to evaluate the effect of EPO on skeletal muscle changes as a complication of type 1 diabetes mellitus in STZ- rat experimental model. Methods: 40 male Sprague Dawely rats were divided into 5 groups: control group , diabetic group (STZ-induced , 50 mg/kg I.P.), insulin treated diabetic ; (received 0.75 IU/ 100g body weight daily, S.C; for 4 weeks) , EPO treated diabetic; (received EPIAO® S.C , 200 I.U/Kg, 3 times weekly, day after day for 4 weeks),and insulin and EPO treated diabetic groups. At the end of the experiments, fasting blood glucose, insulin levels, lipid profile, contractile changes in soleus muscle and glucose transporter 4 (GLUT4) expression in soleus muscle were evaluated. Results: All biochemical parameters were improved in the group treated with insulin or EPO with greater improvement in insulin treated group. The greatest improvement was in the group treated with combined insulin and EPO. Contractile function of soleus muscle in diabetic group showed significant decrease in muscle tension either before or after fatigue, significant decrease in time taken to reach complete fatigue, significant increase in time taken to reach peak and in time taken to relax to 50% when compared with normal group. All parameters were improved in insulin treated and EPO treated groups, with greater improvement in insulin treated group. The greatest improvement was in combined insulin and EPO treated group. The reduced GLUT 4 expression in diabetic soleus muscle was significantly increased in insulin treated group as compared to EPO treated group, however combined EPO and insulin treated group showed greater increase in GLUT4 expression. Conclusion: The present results showed that, EPO injection improved hyperglycemia, hypoinsulinemia, hyperlipidemia, and   skeletal muscle changes observed in STZ-induced diabetes in rats. Therefore, EPO could be beneficial in managing diabetic disorders and the application of EPO in treatment of diabetes can be considered.